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Published on: May 2, 2018
TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages
Zheng Jin1, Zhenhua Zhu2, Shanshan Liu1
1Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Abstract:
Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59Lyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.
Insights
Tripartite motif 59 (TRIM59) deficiency worsens sepsis outcomes by impairing macrophage function and increasing inflammation. Restoring TRIM59 levels may offer a therapeutic strategy for sepsis.
Area of Science:
- Immunology
- Molecular Biology
- Pathology
Background:
- Sepsis, a life-threatening condition, involves bacterial invasion and inflammation.
- Tripartite motif 59 (TRIM59) is implicated in NF-κB signaling and macrophage phagocytosis, but its role in sepsis remains unclear.
Purpose of the Study:
- To investigate the role of TRIM59 in sepsis pathogenesis.
- To elucidate the mechanisms by which TRIM59 influences immune responses during sepsis.
Main Methods:
- Utilized lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) to assess TRIM59 expression.
- Employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate TRIM59's in vivo function.
- Analyzed mortality, immune cell infiltration, organ damage, bacterial burden, cytokine production, and phagocytosis.
Main Results:
- TRIM59 was downregulated in LPS-stimulated BMDMs.
- TRIM59 deficiency (Trim59-cKO mice) led to increased mortality, severe organ damage, and higher bacterial burden in a CLP sepsis model.
- TRIM59 modulated pro-inflammatory cytokine production and macrophage phagocytosis, involving the NF-κB pathway and Fcγ receptors.
Conclusions:
- TRIM59 plays a protective role in sepsis.
- TRIM59 regulates macrophage-mediated inflammation and phagocytosis, crucial for sepsis resolution.
- Targeting TRIM59 may represent a novel therapeutic approach for sepsis.
